Endometrial oestrogen and progesterone receptors and their relationship to sonographic appearance of the endometrium.
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The rapid development of ultrasonographic equipment now permits instantaneous assessment of follicles and endometrium. The sonographic appearance of the endometrium has been discussed in relation to in-vitro fertilization (IVF) cycles. However, a generally agreed view of the relationship of the sonographic appearance to fecundity in IVF cycles has not emerged. We have studied the relationship between steroid receptors and the sonographic appearance of the preovulatory endometrium in natural cycles and ovulation induction cycles. Preovulatory endometrial thickness was not found to be indicative of fecundity, although a preovulatory endometrial thickness of <9 mm related to an elevated miscarriage rate. The preovulatory endometrial echo pattern did not predict fecundity. No relationships were found among endometrial appearance, endometrial steroid receptors and steroid hormone concentrations in serum. Oestrogen or progesterone receptor concentrations were not related to endometrial thickness or to concentrations of serum oestradiol, the only significant correlation being found between the endometrial concentrations of oestrogen and progesterone receptors. The ratio of progesterone:oestrogen receptor concentration was somewhat less in echo pattern B (not triple line) endometrium compared with pattern A (triple line) endometrium. Oestrogen and progesterone receptor concentrations appeared stable on gonadotrophin induction, though fewer numbers were found during clomiphene cycles than in natural cycles. With regard to the distribution of receptor concentration between clomiphene and natural cycles, most women using clomiphene had very low oestrogen receptor populations. Pregnancy rates were low, in spite of high ovulatory rates during clomiphene treatment and were mainly related to low oestrogen receptor concentrations in preovulatory endometrium. (+info)
Nitric oxide in the endometrium.
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Nitric oxide (NO) is an important mediator of paracrine interactions, especially within the vascular system. It is a powerful inhibitor of platelet aggregation and a potent vasodilator. NO is also a neurotransmitter and it plays a role in cell-mediated cytotoxicity. NO-generating enzymes (nitric oxide synthases, NOS) have been described in the endometrium of a number of species, suggesting that NO might be involved in endometrial function. In human endometrium, endothelial NOS and inducible NOS have been localized to glandular epithelium in the non-pregnant uterus. Weak inducible NOS immunoreactivity has been observed in decidualized stromal cells. NO might participate in the initiation and control of menstrual bleeding. Furthermore, it may play a part in the inhibition of platelet aggregation within the endometrium, where menstrual haemostasis is thought to occur primarily by vasoconstriction rather than clot organization. Endometrially derived NO could also suppress myometrial contractility. Recent attention has focused on the part that NO might play in maintaining myometrial quiescence during pregnancy. NO also appears to relax the non-pregnant myometrium, an action which could be exploited for the medical treatment of primary dysmenorrhoea. (+info)
Oxytocin and vasopressin receptors in human and uterine myomas during menstrual cycle and early pregnancy.
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The purpose of this study was to determine the specificity and concentration of oxytocin (OT) and arginine vasopressin (AVP) binding sites in non-pregnant (NP) human and rhesus monkey endometrium, myometrium and fibromyomas, and to determine the cellular localization of OT receptor (OTR). Besides [3H]AVP, [125I]LVA, a specific VP1 receptor subtype antagonist, was used to determine vasopressin receptor (VPR) concentrations. Samples were obtained from 42 pre-menopausal and three pregnant women (5, 13 and 35 weeks gestation), and several NP and pregnant monkeys. Specificity of binding was assessed in competition experiments with unlabelled agonists and antagonists of known pharmacological potency. Cellular localization of OTR was determined by immunohistochemistry. In NP human uterine tissues, [3H]AVP was bound with higher affinity and greater binding capacity than [3H]OT, whereas in pregnant women and in NP and pregnant rhesus monkeys, uterine OT binding capacity was greater. OT and AVP binding sites discriminated very poorly between OT and AVP; [125I]LVA binding sites were more selective than [3H]AVP. Their ligand specificity and binding kinetics indicated the presence of two distinct populations of binding sites for OT and AVP in primate uterus. Endometrium of NP women and monkeys had low OTR and VPR concentrations. Myometrial and endometrial OTR and VPR were down-regulated in midcycle and in early human pregnancy, they were up-regulated in the secretory phase and second half of pregnancy. Immunoreactive OTR in NP uterus was localized in patches of myometrial muscle cells and small numbers of endometrial epithelial cells. (+info)
Regulation of the human oxytocin receptor in the uterus: a molecular approach.
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The oxytocin-oxytocin receptor (OTR) system plays important roles in the human uterus, and the effectiveness of oxytocin is greatly influenced by the pattern of receptor expression in vivo. To investigate OTR expression at the molecular level, we have established a bioassay system for the specific transcripts using Xenopus laevis oocytes, cloned the OTR cDNA, raised anti-OTR antibodies, and characterized OTR genomic clones and systems to study the transcriptional regulation of the gene. Using these molecular tools, we have examined OTR expression in the endometrium and myometrium of non-pregnant and pregnant women. OTR expression appears mainly to be regulated at the transcription level. Analysis of the 5' flanking region of this gene indicates constitutionally active promoter activity when transfected into cultured HeLa and SKN cells. We are currently developing these techniques to analyse OTR regulation in the uterus. (+info)
Desensitization of oxytocin receptors in human myometrium.
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In the present study, we investigated the possible mechanisms by which oxytocin might regulate oxytocin receptor (OTR) density. Exposure of cultured myometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 10(3) binding sites/cell, but this was time-dependently reduced to 20.1 x 10(3) sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR desensitization. (+info)
Expression of the oxytocin receptor in relation to steroid receptors in the uterus of a primate model, the marmoset monkey.
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The dynamics of the receptors for oestrogen (ER), progesterone (PR) and oxytocin (OTR) in the marmoset uterus have been analysed throughout the entire cycle and early pregnancy. Uteri obtained during the early, mid/late and late proliferative phase, and the early, mid and late secretory phase and early pregnancy were examined by immunohistochemistry (OTR, ER, PR) and autoradiography (OTR). A massive upregulation of the ER in the cell nuclei of glandular epithelium and stromal cells during the mid proliferative phase was succeeded by a declining staining intensity and positively stained cell number in the secretory phase. PR immunoreactivity increased in the late proliferative phase and early secretory phase, mainly within the cell nuclei, and then declined in both intensity and cell number towards the mid to late secretory phase. Myometrium showed a similar staining pattern for the steroid receptors. OTR were expressed weakly in stroma throughout the entire cycle, increasing slightly in the secretory phase. Glandular epithelium showed positive staining only during the periovulatory period. Myometrial OTR expression was weak during the proliferative phase, increased towards the secretory phase, and was maximal in the late secretory phase. Myometrial tissue adjacent to endometrium was most strongly stained. A cyclic shift evidently occurred in the pattern of steroid receptors, perhaps reflecting the steroid environment or the luteinizing hormone increase associated with ovulation. (+info)
Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography.
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The transport function of the uterus and oviducts and its modulation by oxytocin has been examined using hysterosalpingoscintigraphy, recording of intrauterine pressure, electrohysterography and Doppler sonography of the Fallopian tubes. After application to the posterior vaginal fornix, a rapid (within minutes) uptake of the labelled particles into the uterus was observed during the follicular and during the luteal phase of the cycle in all patients. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Transport was directed predominantly into the tube ipsilateral to the ovary bearing the dominant follicle; the contralateral oviduct appeared to be functionally closed. The proportion of patients exhibiting ipsilateral transport did increase concomitant with the increase of the diameter of the dominant follicle. That ipsilateral transport has biological significance is suggested by the observation that the pregnancy rate following spontaneous intercourse or insemination was significantly higher in those women in whom ipsilateral transport could be demonstrated than in those who failed to exhibit lateralization. Oxytocin administration was followed by a dramatic increase in the amount of material transported to the ipsilateral tube, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. Continuous recording of intrauterine pressure before and after oxytocin administration did show an increase in basal tonus and amplitude of contractions and a reversal of the pressure gradient from a fundo-cervical to a cervico-fundal direction. These actions of oxytocin were accompanied by an increase in amplitude of potentials recorded by electrohysterography. These data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle. In addition, they strongly suggest a critical role of oxytocin in this process. Failure of this mechanism appears to be a cause of subfertility or infertility, as indicated by the low pregnancy rate following intrauterine insemination or normal intercourse in the presence of patent Fallopian tubes. It may be regarded as a new nosological entity for which we propose the term tubal transport disorder (TTD). Since pregnancy rate of such patients is normal when treated with in-vitro fertilization (IVF), hysterosalpingoscintigraphy seems to be useful for the choice of treatment modalities in patients with patent Fallopian tubes suffering from infertility. (+info)
Control and assessment of the uterus and cervix during pregnancy and labour.
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Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments. (+info)